EP0030209B1 - Procédé de préparation de 1H-1,2,4-triazole - Google Patents

Procédé de préparation de 1H-1,2,4-triazole Download PDF

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Publication number
EP0030209B1
EP0030209B1 EP80810333A EP80810333A EP0030209B1 EP 0030209 B1 EP0030209 B1 EP 0030209B1 EP 80810333 A EP80810333 A EP 80810333A EP 80810333 A EP80810333 A EP 80810333A EP 0030209 B1 EP0030209 B1 EP 0030209B1
Authority
EP
European Patent Office
Prior art keywords
formamide
hydrazine
triazole
reaction
process according
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Expired
Application number
EP80810333A
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German (de)
English (en)
Other versions
EP0030209A1 (fr
Inventor
Harris E. Petree
Joseph R. Pociask
John T. Gupton
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Novartis AG
Original Assignee
Ciba Geigy AG
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Ciba Geigy AG filed Critical Ciba Geigy AG
Priority to AT80810333T priority Critical patent/ATE6367T1/de
Publication of EP0030209A1 publication Critical patent/EP0030209A1/fr
Application granted granted Critical
Publication of EP0030209B1 publication Critical patent/EP0030209B1/fr
Expired legal-status Critical Current

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Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D249/00—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms
    • C07D249/02—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms not condensed with other rings
    • C07D249/08—1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles

Definitions

  • the present invention relates to a process for the preparation of 1H-1,2,4-triazole by reacting hydrazine and formamide.
  • 1H-1,2,4-triazole is a valuable intermediate for the production of crop protection agents, especially fungicides.
  • crop protection agents especially fungicides.
  • Such agents, their manufacture and use are described in US-A-3912752 and US-A-4079062.
  • a process for the preparation of 1H-1,2,4-triazole is also known, in which formamide and hydrazine hydrate are reacted at 100-250 ° C. in a molar ratio of 1: to 1 2.7 in the presence of ammonia.
  • the process is carried out in a three-stage cascade, in the first stage at 100-120 ° C, in the second stage at 180-200 ° C and in the third stage at 210-230 ° C and that at 110-140 ° C condensable volatile reaction products of the second stage in the second stage and the liquid reaction products condensable at 4080 ° C of the third stage in the first stage.
  • 1H-1,2,4-triazole is obtained in a yield of 93-94% of theory and in a purity of 90-98% (DE-A-2 802 491).
  • 1 H-1,2,4-triazole is prepared by reacting hydrazine in anhydrous or water-containing form with formamide at elevated temperature, the molar ratio of formamide to hydrazine being at least 2.5: 1.
  • the process is characterized in that the hydrazine is introduced into the formamide preheated to 160-180 ° C at such a rate that the reaction temperature is maintained, the by-products formed, water, ammonia and formic acid are separated off directly during the reaction by distillation, the reaction mixture after the addition of the hydrazine has ended, holds at reaction temperature for 1-2 hours, then the unreacted formamide is distilled off and the 1H-1,2,4-triazole is obtained as residue.
  • anhydrous hydrazine is difficult to produce and, because of its lower stability at the reaction temperatures used according to the invention and its toxic properties, is difficult to handle, the use of water-containing hydrazine is preferred.
  • the water content of the hydrazine can be 10-50% by weight. Hydrazine hydrate has proven to be particularly advantageous since, due to its composition, it can be regarded as a 64% solution of hydrazine in water.
  • the molar ratio of formamide to hydrazine is at least 2.5: 1.
  • the molar ratio of formamide to hydrazine is preferably at least 4: 1.
  • the size of the molar excess of formamide is not itself critical for the course of the process. It is primarily determined from an economic point of view, since with an increasing molar ratio of formamide to hydrazine, the amount of formamide to be separated off by distillation after completion of the reaction, and thus the energy required to carry out the process, increases. In practice, it has proven advantageous to use molar ratios of formamide to hydrazine which are between 4: 1 and 8: 1. The use of molar ratios of formamide to hydrazine of 4.5: 1 to 6: 1 is particularly advantageous.
  • the method according to the invention is carried out at temperatures of 160-180 ° C.
  • the process can in principle also be carried out at lower and higher temperatures, but at temperatures below 160 ° C. with considerably longer reaction times and at temperatures above 180 ° C. with increasing decomposition of formamide.
  • a reaction temperature of 168-172 ° C has proven to be particularly advantageous.
  • the 1H-1,2,4-triazole can be obtained from the excess formamide after the water has been separated off by crystallization.
  • the formamide adhering to the 1H-1,2,4-triazole after crystallization can be removed by washing with a suitable organic solvent, such as methyl ethyl ketone, tetrahydrofuran or ethyl acetate. In this way, however, only 40-50% of the 1H-1,2,4-triazole present in the reaction mixture can be separated off, so that there is a need to recycle the hydrate containing 1H-1,2,4-triazal.
  • the 1H-1,2,4-triazole is preferably isolated in such a way that the excess formamide is distilled off by distillation under reduced pressure, for example at 20-100 torr.
  • a fraction with a boiling range of 95-110 ° C. at 20-30 torr is first obtained, which contains only about 30% formamide.
  • About 70% of the formamide contained therein can be obtained from this fraction by redistillation.
  • the second fraction with a boiling range of 110-135 ° C at 20-30 Torr contains about 85% formamide and is directly suitable for further reaction with hydrazine.
  • This 85% formamide contains, in addition to about 1% 1 H-1,2,4-triazole, essentially water, formic acid and ammonium formate as impurities.
  • vacuum distillation is the most economical form of working up the reaction mixture.
  • the 1 H-1,2,4-triazole can be obtained from this solvent either by pouring the melt directly onto a cooled surface and comminuting the solidified melt or by adding a suitable solvent and crystallizing it Crystallization the purer product is obtained.
  • the direct extraction of the 1H-1,2,4-triazole from the melt is a very simple operation. There are no losses in yield, and no further materials are added to the 1H-1,2,4-triazole.
  • the triazole obtained directly from the melt is usually 94% and contains 0.5-1.2% 4-formamidino-1,2,4-triazole and 0.3-0.4% 4-amino-1,2, 4-triazole. Other contaminants such as water, formic acid and formamide are present in a total amount of less than 0.6%.
  • the 1H-1,2,4-triazole is obtained from the melt, there is no appreciable decomposition of the product. The color of the product varies from light brown to dark brown or reddish brown.
  • the formamide can be distilled off at lower pressure and temperature.
  • the discoloration of the product can also be reduced by continuous distillation, since there is less decomposition.
  • the 94% 1H-1,2,4-triazole obtained from the melt is directly suitable for the synthesis of fungicidal and microbicidal active ingredients and other pesticides.
  • the 1H-1,2,4-triazole can be obtained in a purer form if the melt obtained after the formamide has been evaporated is recrystallized from a suitable solvent. Suitable solvents are, for example, ethyl acetate, tetrahydrofuran, methyl ethyl ketone and formamide.
  • the 1H-1,2,4-triazole obtained by crystallization is 96-98% pure and contains less than 0.3% 4-formamidino-1,2,4-triazole and less than 0.1% 4-amino-1 , 2,4-tri-azpl.
  • the 1H-1,2,4-triazole is obtained in an average yield of 87% of theory.
  • a further 9% of theory of 1H-1,2,4-triazole can be obtained from the mother liquor.
  • the solvent is distilled off from the mother liquor and the residue is slurried in tetrahydrofuran or methyl ethyl ketone and filtered. In this way, about 70% of the 1H-1,2,4-triazole present in the mother liquor is obtained.
  • the 1H-1,2,4-triazole can be obtained in a yield of 93-95% of theory by crystallization when working up the mother liquor.
  • formamide is heated to 168 172 ° C. and hydrazine hydrate is introduced at this temperature for 2-4 hours with stirring below the surface of the formamide, the molar ratio of formamide to hydrazine being at least 4: 1, distilled off the by-products water, ammonia and formic acid immediately during the reaction and then removed the excess formamide by vacuum distillation and won the 1H-1,2,4-triazole as a melt.
  • the process according to the invention makes it possible to prepare 1H-1,2,4-triazole in a simple manner in very good yield and purity from formamide and hydrazine.
  • the procedure according to the invention largely avoids the formation of undesired by-products, such as 4-amino-1,2,4-triazole and 4-formamidino-1,2,4-triazole, when using a relatively small excess of formamide.
  • the procedure according to the invention is made possible by using small excesses of formamide.
  • reaction mixture temperature is kept another 1 1/2 hours at 170 ° C. Then the reaction mixture is cooled to room temperature. 1200-1250 g of a yellowish solution are obtained, which crystallizes on standing. The solution obtained contains 4245% 1 H-1,2,4-triazole, which corresponds to an in situ yield of 95-98% of theory.
  • the reaction vessel described in section a) is connected to a vacuum distillation apparatus after stirring the reaction mixture at 170 ° C. for 11 ⁇ 2 hours, and the formamide is distilled off at 20 torr (15 mbar).
  • the first fraction obtained is 150-175 ml of distillate, which passes at 105-110 ° C. This fraction contains about 30% formamide.
  • the distillation is continued and 350-400 ml of distillate with a boiling point of 115-120 ° C. are obtained as the second fraction. Now the heating is interrupted to prevent the temperature of the residue from rising above 130 ° C.
  • a melt of crude 1H-1,2,4-triazole obtained by the method described in section b) is cooled to about 80 ° C and in the reaction vessel after adding a sufficient amount of a solvent, such as methyl ethyl ketone, tetrahydrofuran, ethyl acetate or formamide, under Warm and stir completely dissolved.
  • the solution obtained is then cooled to 10 ° C., resulting in a crystal slurry from which the crystalline 1H-1,2,4-triazole is separated off by filtration. After drying, 480-510 g of a brownish to reddish product containing 96-98% 1H-1,2,4-triazole are obtained, which corresponds to a yield of 84-90% of theory.
  • a second fraction of 1 H-1, 2,4-triazole can be obtained from the mother liquor by evaporation of part of the solvent, which is filtered off and washed with tetrahydrofuran or methyl ethyl ketone. This way with a total yield of 92-94% of theory 1H-1,2,4-triazole obtained can either be used as such or further purified.

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Pretreatment Of Seeds And Plants (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Saccharide Compounds (AREA)

Claims (9)

1. Procédé de préparation de 1H-1,2,4-triazole par réaction d'hydrazine sous forme anhydre ou aqueuse avec du formamide à température accrue, le rapport molaire du formamide à l'hydrazine s'élevant à au moins 2,5 : 1, caractérisé en ce qu'on introduit l'hydrazine dans le formamide préalablement chauffé à 160-180°C avec une vitesse telle que la température de la réaction reste constante, en ce qu'on sépare par distillation les produits secondaires eau, ammoniac et acide formique formés immédiatement pendant la réaction, en ce qu'on maintient le mélange réactionnel à la température de la réaction pendant 1 à 2 h après la fin de l'addition de l'hydrazine, puis en ce qu'on sépare par distillation le formamide n'ayant pas réagi et en ce qu'on obtient comme résidu le 1H-1,2,4-tria- zole.
2. Procédé selon la revendication 1, caractérisé en ce qu'on utilise l'hydrazine sous la forme de son hydrate.
3. Procédé selon la revendication 1, caractérisé en ce qu'on utilise le formamide et l'hydrazine dans un rapport molaire compris entre 4: 1 et 8:1.
4. Procédé selon les revendications 1 et 3, caractérisé en ce qu'on utilise le formamide et l'hydrazine dans un rapport molaire compris entre 4,5 : 1 et 6 : 1.
5. Procédé selon la revendication 1, caractérisé en ce qu'on introduit l'hydrazine pendant 2 à 4 h en-dessous de la surface du formamide chauffé à la température de la réaction.
6. Procédé selon la revendication 1, caractérisé en ce qu'on conduit la réaction du formamide et de l'hydrazine à une température de 168-172°C.
7. Procédé selon la revendication 1, caractérisé en ce qu'après la fin de la réaction on distille l'excès de formamide à une pression réduite.
8. Procédé selon la revendication 1, caractérisé en ce qu'après la séparation de l'excès de formamide par distillation on recristallise le produit brut obtenu à partir de l'acétate d'éthyle, du tétrahydrofuranne, de la méthyléthylcétone ou du formamide.
9. Procédé selon la revendication 1, caractérisé en ce qu'on chauffe le formamide à 168-172°C et en ce qu'à cette température on introduit pendant 2 à 4 h tout en agitant de l'hydrazine hydratée en-dessous de la surface du formamide, le rapport molaire du formamide à l'hydrazine hydratée s'élevant à au moins 4 : 1, et en ce qu'on sépare l'excès de formamide par distillation sous vide.
EP80810333A 1979-11-07 1980-11-03 Procédé de préparation de 1H-1,2,4-triazole Expired EP0030209B1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
AT80810333T ATE6367T1 (de) 1979-11-07 1980-11-03 Verfahren zur herstellung von 1h-1,2,4-triazol.

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US92257 1979-11-07
US06/092,257 US4267347A (en) 1979-11-07 1979-11-07 Method for direct preparation for 1,2,4-triazole from hydrazine and formamide

Publications (2)

Publication Number Publication Date
EP0030209A1 EP0030209A1 (fr) 1981-06-10
EP0030209B1 true EP0030209B1 (fr) 1984-02-22

Family

ID=22232407

Family Applications (1)

Application Number Title Priority Date Filing Date
EP80810333A Expired EP0030209B1 (fr) 1979-11-07 1980-11-03 Procédé de préparation de 1H-1,2,4-triazole

Country Status (8)

Country Link
US (1) US4267347A (fr)
EP (1) EP0030209B1 (fr)
JP (1) JPS5928549B2 (fr)
AT (1) ATE6367T1 (fr)
BR (1) BR8007200A (fr)
CA (1) CA1157869A (fr)
DE (1) DE3066717D1 (fr)
IL (1) IL61419A (fr)

Families Citing this family (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS5689952U (fr) * 1979-12-13 1981-07-18
AT369736B (de) * 1980-07-07 1983-01-25 Loba Chemie Verfahren zur herstellung von 1,2,4-triazol
FR2521558A1 (fr) * 1982-02-18 1983-08-19 Nehezvegyipari Kutato Intezet Procede pour la preparation de 1, 2, 4-triazole
US4490539A (en) * 1982-06-22 1984-12-25 Nehezvegyipari Kutato Intezet Process for the preparation of 1,2,4-triazole
DE3245110A1 (de) * 1982-12-07 1984-06-07 Basf Ag, 6700 Ludwigshafen Verfahren zur herstellung von 1,2,4-triazol
HU195790B (en) * 1983-12-21 1988-07-28 Alkaloida Vegyeszeti Gyar Process for producing 1,2,4-triazol
DE69934544T2 (de) * 1998-05-12 2007-04-26 Mitsubishi Gas Chemical Co., Inc. Verfahren zur Herstellung von 1,2,4-Triazolen ausgehend von Ketazinen
KR100327818B1 (ko) * 1999-04-16 2002-03-09 윤재승 플루코나졸의 제조방법
CN102674394B (zh) * 2012-05-09 2016-09-28 湖南太阳植物资源有限公司 一种1h-1，2，4三氮唑副产氨水回收利用的方法
CN104693132B (zh) * 2014-12-30 2017-07-14 衡阳师范学院 一种1h‑1,2,4三氮唑循环母液回收利用的方法

Family Cites Families (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
LU61617A1 (fr) * 1969-09-03 1970-12-01
DE2802491B2 (de) * 1978-01-20 1980-10-30 Bayer Ag, 5090 Leverkusen Verfahren zur Herstellung von 1,2,4-Triazol

Also Published As

Publication number Publication date
JPS5928549B2 (ja) 1984-07-13
JPS5681570A (en) 1981-07-03
EP0030209A1 (fr) 1981-06-10
DE3066717D1 (en) 1984-03-29
IL61419A (en) 1985-01-31
BR8007200A (pt) 1981-05-19
IL61419A0 (en) 1980-12-31
US4267347A (en) 1981-05-12
ATE6367T1 (de) 1984-03-15
CA1157869A (fr) 1983-11-29

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